Tafenoquine is a 8-aminoquinoline currently being developed by SmithKline Beecham (SB) and the Walter Reed Army Institute of Research (WRAIR) for malaria prophylaxis in adults. Phase II clinical studies in adults have shown that weekly and monthly dosing regimens of tafenoquine are highly efficacious for malaria prevention (including multi-drug resistant plasmodium species). One and 3-day adult regimens of tafenoquine are also efficacious for the radical cure (elimination of relapsing liver stages) of Plasmodium vivax. There is a need for the development of a pediatric formulation of tafenoquine. Children, who are at high risk for the consequences of this infection, can potentially benefit the most from this drug. Pediatric drug development, an important public health indication, is not a funding priority for the US Department of Defense. Given adequate funding, SB and the US Army have the necessary resources to develop tafenoquine for public health indications, which include malaria prophylaxis in children (a required first step before additional pediatric investigations such as radical cure of P. vivax and transmission blocking). The first aim of this proposal is to achieve US Food and Drug Administration (FDA) approval of a new pediatric formulation of tafenoquine for malaria prophylaxis in children. Furthermore, we intend to provide initial "proof of concept" that tafenoquine has the potential to interrupt malaria transmission and radically curses infections of P. vivax in children. First, a pediatric suspensions will be developed, and compared with the available capsule formulation in a Phase I relative bioavailability clinical trial in adult volunteers. Then, a Phase II population pharmacokinetic (PK) study will be conducted in hospitalized P. vivax infected children. This study will determine which pediatric doses of tafenoquine provide comparable concentrations to those in adults, and will evaluate safety in this at risk population. This study will determine which pediatric doses of tafenoquine provide comparable concentrations to those in adults, and will evaluate safety in this at risk population. This study will also assess the ability of tafenoquine to radically cure P. vivax in children. Finally, a Phase III pivotal malaria prophylaxis field adult safety and efficacy data, will lead to regulatory approval of a pediatric malaria prophylaxis indication for tafenoquine. In parallel with the last two clinical trials, it is intended to conduct a "proof of concept" malaria transmission-blocking study. Once completed, this project, if successful, will yield the following: 1) A pediatric formulation of tafenoquine radically cures P. vivax infections in children, and 4) Initial "proof of concept" that administration of tafenoquine of transmission blocking.